Hyperthermia (41-43 degrees centigrade) can cause regression of cancer in animals and man and perhaps the acquisition of thermosensitivity occurs with transformation of normal tissue to neoplastic tissue. This hyperthermic effect can be enhanced by chemotherapy. Thermochemotherapy therefore could become worthy of clinical trial. Before attempting this type of therapy a sound scientific basis for use of hyperthermia as an adjuvant to chemotherapy must be established. Isolated organ (liver) perfusion is a model system in which this therapy can be studied. Demonstration of the safety and efficacy of thermochemotherapy for cancer by isolated liver perfusion is the ultimate goal of the proposed research plan. The following studies will be conducted utilizing the isolated in situ rat liver perfusion system in which the criteria of function and viability have been defined: (1) The effects of hyperthermia on the perfused liver functions: oxygen consumption, gluconeogenesis, urea, protein and nucleic acid synthesis will be determined; (2) A surgical technique will be developed in order to study animal survival and clearly identify the limits of tolerance to hyperthermic perfusion; (3) The effect of several individual antineoplastic drugs (melphalan, actinomycin D, 5-fluorouracil, cordycepin, 4(5)-(3,3-dimethyl-1-triazeno) imidazole-5(4)-carboxamide, bleomycin, and adriamycin) on the above liver functions will be studied; (4) The effects of hyperthermia alone and with the individual antitumor agents on protein and nucleic acid synthesis in the isolated perfused regenerating rat liver will be studied; and (5) Similar data as in aim #4 will be obtained using intrahepatic transplanted tumor for study and determining effect of treatment on animal survival.